Mouse CCL8, a CCR8 agonist, promotes atopic dermatitis by recruiting IL-5+ TH2 cells

被引：239

作者：

Islam, Sabina A. ^{[1
]}

Chang, Daniel S. ^{[1
]}

Colvin, Richard A. ^{[1
]}

Byrne, Mike H. ^{[1
]}

McCully, Michelle L. ^{[2
]}

Moser, Bernhard ^{[2
]}

Lira, Sergio A. ^{[3
]}

Charo, Israel F. ^{[4
]}

Luster, Andrew D. ^{[1
]}

机构：

[1] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Rheumatol Allergy & Immunol,Ctr Immunol & Inf, Boston, MA 02163 USA

[2] Cardiff Univ, Dept Infect Immun & Biochem, Cardiff, S Glam, Wales

[3] Mt Sinai Sch Med, Inst Immunol, New York, NY USA

[4] Univ Calif San Francisco, Gladstone Inst Cardiovasc Dis, San Francisco, CA 94143 USA

来源：

NATURE IMMUNOLOGY | 2011年 / 12卷 / 02期

基金：

美国国家卫生研究院;

关键词：

CHEMOKINE RECEPTOR CCR8; T-CELLS; DENDRITIC CELLS; AIRWAY INFLAMMATION; IMMUNE-RESPONSES; CUTTING EDGE; TH1; CELLS; IN-VIVO; EXPRESSION; DIFFERENTIATION;

D O I：

10.1038/ni.1984

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Mouse CCL8 is a CC chemokine of the monocyte chemoattractant protein (MCP) family whose biological activity and receptor usage have remained elusive. Here we show that CCL8 is highly expressed in the skin, where it serves as an agonist for the chemokine receptor CCR8 but not for CCR2. This distinguishes CCL8 from all other MCP chemokines. CCL8 responsiveness defined a population of highly differentiated, CCR8-expressing inflammatory T helper type 2 (T(H)2) cells enriched for interleukin (IL)-5. Ccr8- and Ccl8-deficient mice had markedly less eosinophilic inflammation than wild-type or Ccr4-deficient mice in a model of chronic atopic dermatitis. Adoptive transfer studies established CCR8 as a key regulator of T(H)2 cell recruitment into allergen-inflamed skin. In humans, CCR8 expression also defined an IL-5-enriched T(H)2 cell subset. The CCL8-CCR8 chemokine axis is therefore a crucial regulator of T(H)2 cell homing that drives IL-5-mediated chronic allergic inflammation.

引用

页码：167 / U86

页数：13

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